Histone deacetylases inhibitors as new potential drugs against Leishmania braziliensis, the main causative agent of New World Tegumentary Leishmaniasis.

Histone deacetylases inhibitors as new potential drugs against Leishmania braziliensis, the main causative agent of New World Tegumentary Leishmaniasis. Biochem Pharmacol. 2020 Aug 07;:114191 Authors: Ângelo de Souza L, Silva E Bastos M, de Melo Agripino J, Souza Onofre T, Fanny Apaza Calla L, Heimburg T, Ghazy E, Bayer T, Hugo Ferraz da Silva V, Dutra Ribeiro P, Licursi de Oliveira L, Costa Bressan G, Rogéria de Almeida Lamêgo M, Silva-Júnior A, de Souza Vasconcellos R, Márcia Suarez-Fontes A, Almeida-Silva J, André Vannier-Santos M, Pierce R, Sippl W, Lopes Rangel Fietto J Abstract The protozoan parasite Leishmania braziliensis is a major causative agent of the neglected tropical diseases Cutaneous and Mucocutaneous Leishmaniases in the New World. There are no vaccines to prevent the infection and the treatment relies on few drugs that often display high toxicity and costs. Thus, chemotherapeutic alternatives are required. Histone Deacetylases (HDACs) are epigenetic enzymes involved in the control of chromatin structure. In this work, we tested an in-house library of 78 hydroxamic acid derivatives as putative inhibitors of L. braziliensis HDACs (HDACi). The compounds were evaluated in relation to the toxicity to the host cell macrophage and to the leishmanicidal effect against L. braziliensis during in vitro infection. Eight HDACi showed significant leishmanicidal effects and the top 5 compounds showed effective concentration...
Source: Biochemical Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Biochem Pharmacol Source Type: research